Excitable cells in tissues (e.g., nervous, cardiac, or muscular tissue) can be modulated by electric fields, in that way providing a possible therapeutic approach for several disorders affecting these tissues. An example may be chronic deep brain stimulation (DBS), a treatment for symptoms of many disorders, such as movement disorders (e.g., essential tremor, posttraumatic tremor, tremor in multiple sclerosis, dystonia), epilepsy, chronic pain, etc. Taking the example of DBS for akinesia, i.e., the inability to start a movement, which is one of the symptoms of Parkinson's disease.
DBS comprises implantation of an electrode 1, which is preferably a multi-electrode, connected to a lead 2 into the subthalamic nucleus (STN), which is a co-ordinating motor center through which incoming nerve impulses are directed to appropriate parts of the globus pallidus. Furthermore, a pulse generator or stimulator 3 is required to which the lead 2 is connected through an extension wire 4 and which is surgically implanted under the skin, e.g., in the upper chest of a patient. This is illustrated in FIG. 1.
The extension wire 4 is threaded from the electrode lead 2 from the scalp area under the skin to the chest where it is connected to the pulse generator or stimulator 3. To turn it on and off, the patient passes a hand-held magnet over the pulse generator or stimulator 3. For example, the pulse generator or stimulator 3 may be turned off at night. In the on-position, the pulse generator or stimulator 3 produces a high-frequency, pulsed electric current that is sent along the electrode to the STN. The electrical stimulation in the STN takes away the akinesia. The stimulus parameters can be adjusted to provide the best response and minimize adverse reactions.
A disadvantage of the above-described system is that the pulse generator or stimulator 3 has to be replaced to change batteries, which, theoretically, should last 5 years. However, in practice, the batteries last much less. Sometimes they have to be replaced every year. This is unpleasant for the patient because a local incision at the stimulator location is required. Furthermore, it is expensive for the health care system.
Currently, in surgical practice, a medical device called the Activa® Tremor Control System, manufactured by Medtronics Inc., is used, which has a good success rate when compared to standard medications. Furthermore, a line of neurological pulse generators similar to Activa® has been produced by Medtronics Inc.
The Activa® Tremor Control System device provides electrical pulses to precisely targeted areas of the brain. It can be compared to a cardiac pacemaker. This system, which is fully implantable, consists of an insulated microwire (lead) terminated in 4 electrodes to be implanted in the STN, connected via an insulated wire with a pulse generator device placed underneath the skin in the chest or abdomen. This device generates the electrical pulses necessary for the stimulation. Although highly effective for the large majority of the Parkinson patients, clinical application of DBS (Activa® Therapy provided by Medtronic) shows a wide range of outcomes.
The device implantation is performed by a functional stereotactic neurosurgeon, that is, a neurosurgeon that specializes in treating central nervous system function disorders using stereotactic techniques. This means that a stereotactic head frame is used to keep the patient's head still during surgery and the neurosurgeon uses imaging techniques such as magnetic resonance imaging (MRI) or computed topography (CT) to map the brain and locate the position of the site to be stimulated (anatomic target).
An essential part of the implantation of the DBS electrode is the physiological test stimulation when the electrode is approaching the anatomical target. To verify the efficacy of the stimulation, the full cooperation of an awake patient is required. However in many cases, the cooperation with the patient is not sufficient to achieve optimally functional brain target and, therefore, microelectrode-based recordings of the cellular activity in and around the intended functional brain target can be used in order to overcome the need for the patient cooperation. Currently, a microelectrode recording procedure is used intra-operatively to identify the boundaries of the STN. This procedure makes use of five parallel microelectrode trajectories in a rectangular grid, which explores the brain structure in discrete steps of 0.5 mm.
To help the clinician place the DBS electrode and decide which stimulation sites to use, it could be valuable to define the anatomical location of each stimulation site relative to the target structure. This information is currently difficult to obtain because of the limited resolution of the imaging techniques as well as due to individual variations in the position of individual brain structures. Signal recording with high spatial resolution and high signal to noise ratio as well as signal analysis that would enable automatic recognition of the functional brain target would therefore enable the optimization and standardization of the therapy. Moreover, chronically implanted microelectrodes should provide an effective follow up procedure after the implantation, by actively enabling to adjust the stimulation parameters in order to adapt to possible movement of the implanted device in respect to the relevant brain structures.
One of the systems of Medtronics Inc. is described in U.S. Patent Publication No. 2002/0022872. This document provides a lead for brain stimulation which is capable of micro single cell recording and macro test stimulation. Such lead is illustrated in FIG. 2. The lead 10 comprises a macro-segment 5 and a micro-segment 6; the macro-segment 5 having a length that is longer than the length of the micro-segment 6. The macro-segment 5 most preferably comprises a lead casing 7. A macro-electrode 8 is positioned at the distal end of the casing 7 and conductors 9. The micro-segment 6 most preferably comprises a micro-electrode 11 encapsulated within an insulating layer. The micro-electrode 11 has, at its exposed tip, an electrode surface area less than about 500 μm2, and even more preferably an electrode surface area less than 1 μm2 for single cell recording applications. In the device described in U.S. Patent Publication No. 2002/0022872, the macro-electrodes are used for stimulation, i.e., to deliver stimulation pulses, while the micro-electrode at the tip of the micro-segment is used for recording.
However, the system described in U.S. Patent Publication No. 2002/0022872 only has four positions from which to perform measurements (four macro-electrodes 8). This only makes it possible to measure in the length of the probe. Furthermore, the system cannot be used for chronic stimulation. Therefore, the system has to be removed and replaced by a conventional DBS lead.
Few groups in the world are attempting to use micromachining techniques in order to fabricate multi-site recording probes to be implemented in cortical prostheses.
Michigan University has provided a probe, in the further description referred to as ‘Michigan probe’. FIGS. 3A, 3B, and 3C illustrate examples of 2D needle probes, and FIG. 3D illustrates an example of a 3D multi-site needle probe. A Michigan probe comprises a plurality of needles and a large number of recording sites, formed by passive iridium electrodes placed along the shaft of each needle (see FIG. 3). This makes it possible to record electrical activity at different depths in the cortex. Designed for monkey recordings, the length of each needle in a probe is around 3.8 mm with the shank tips spaced at ˜150 um. Readout electronics have been integrated at the probe terminal opposite to recording tip. The main challenge with the Michigan probe is represented by the creation of 3D arrays starting from 2D probes, namely the transfer of the 2D probes onto the supporting platform. This is currently done by micro-assembly as illustrated in FIG. 4.
A different approach is proposed by Utah University. Their 3D probe, further referred to as ‘Utah probe’ and illustrated in FIG. 5, consists of a 10×10 array of needles having a single recording site at the tip. With only one recording site at a fixed cortical depth, the Utah probe suffers from the same placement problems as microwires.
Motta, P. S. and Judy, J. W., have described a method for the fabrication of micromachined probes for deep-brain stimulation (“Micromachined probes for deep brain stimulation”, 2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology”, May 2-4, 2002, Wisconsin USA, Proceedings pp. 251-254). Their method makes use of the electroplating technique to create a probe with a microwire-like geometry with a tapering diameter. This probe comprises stimulation electrodes only, and no recording sites. It only allows depth modulation of the stimulation field and no 3D distribution.
The common problem with chronically implanted electrodes is that of the tissue-electrode interface. Any object inserted in the brain causes brain damage, disrupted blood vessels and microhemorrhage. Neurons are sliced or ripped as the electrode is inserted. Under these conditions glial cells begin to proliferate and form a loose encapsulation around the electrode at a considerable distance (100-200 μm). Chronically, this results in an increase of the electrode impedance, which leads to high electrical noise and poor quality recordings.
The size and the shape of the electrode and the way it is inserted are critical factors for the type of damage to be produced. All the prior art literature focuses on nail-like electrode shape, based on the assumption that small nail tip size will result in minimal tissue damage. However, the brain is continuously moving and in some cases when mechanical shocks may occur, these nails may act like micro-knifes and section the blood vessels.